The renal proximal tubule actively secrets many organic anions. It is generelly accepted that the baso-lateral membrane constitutes the active, carrier-mediated step in the transepithelial movement of organic anions, e.g., p-aminohippurate (PAH). However, the chemical nature of the carrier(s) is entirely unknown at present. We have recently characterized the specific inhibitory effect of 4-acetamido-4'-isothiocyano-2,2' disulfonic acid stilbene (SITS) on PAH uptake in the kidney slice. Extending this we propose to investigate the interaction of two probes of organic anion transport which may covalently bind at or near the transport site. The first of these is an analogue of the stilbene mentioned above, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS), which is known to covalently link to membrane protein. The second is a photoaffinity probe, N-(4-azido-2-nitrophenyl)-2-amino ethyl sulfonate (NAP-taurine), an azido derivative of the amino acid taurine. This compound may be transported on the organic anion carrier. Upon exposure to light it is converted to a highly reactive nitrene, which covalently attaches to protein proximate to its location at the time of light exposure. Thus, it should be possible to photo activate this compound while it is bound to its transport site. We have also demonstrated that this compound inhibits PAH transport. Initially the inhibitory effect of these anionic probes on the transport of PAH will be characterized further in the cortical slice, isolated tubule and isolated perfused kidney. Subsequently, the interaction of these probes with the tissue will be investigated viz., the permeability and nature of binding. Finally, an attempt will be made to label the transport site(s) with DIDS, and NAP-taurine, and then identify and isolate the labeled membrane proteins using ultracentrifugation and gel electrophoresis. Such labeled protein may represent specific carriers responsible for the translocation of organic anions across the baso-lateral membrane.